Field
The present disclosure relates to crystalline forms of {[1-cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid (Compound A), the process of preparing crystalline forms of Compound A, the pharmaceutical compositions containing them, and the methods of use thereof.
State of the Art
{[1-Cyano-5-(4-chlorophenoxy)-4-hydroxy-isoquinoline-3-carbonyl]-amino}-acetic acid (hereinafter, Compound A) is a potent inhibitor of hypoxia inducible factor (HIF) prolyl hydroxylase. HIF prolyl hydroxylase inhibitors are useful for increasing the stability and/or activity of HIF, and useful for treating and preventing disorders associated with HIF, including anemia, ischemia, and hypoxia. U.S. Pat. No. 7,928,120, which is incorporated herein in its entirety, describes a family of compounds that encompasses Compound A, including their structures, syntheses and methods of use.
A compound can exist in one or more crystalline forms. Crystalline forms of a drug substance can have different chemical and physical properties, including melting point, chemical reactivity, solubility, dissolution rate, optical and mechanical properties, vapor pressure, hygroscopicity, particle shape, density, flowability, and compatibility. These properties can have a direct effect on the ability to process and/or manufacture a compound as a drug product. Crystalline forms can also exhibit different stabilities and bioavailability. The most stable crystalline form of a drug product is often chosen during drug development based on the minimal potential for conversion to another crystalline form and on its greater chemical stability. To ensure the quality, safety, and efficacy of a drug product, it is important to choose a crystalline form that is stable, is manufactured reproducibly, and has favorable physicochemical properties. Therefore provided herein, are crystalline forms of Compound A, which can be manufactured as a drug product, and can be used to treat, and prevent HIF-associated disorders including conditions involving anemia, ischemia, and hypoxia.